Could popping a pill bring someone similar benefits to running on a treadmill or doing resistance training? In new research, scientists moved one step closer to making this a reality and developing a drug that can mimic some of the cellular effects of exercise.

The goal is to make a drug that flips switches in human cells that would normally be activated by exercise. These switches help maintain and regenerate muscle mass and boost the activity of cells' power houses, for example, said principal investigator Bahaa Elgendy, an associate professor of medicinal chemistry and anesthesiology at Washington University School of Medicine in St. Louis.

Being able to trigger these cellular changes without exercise would be useful for older people, people with muscle-wasting disorders and those who might lose muscle mass while taking weight-loss-inducing drugs, such as Ozempic, he told Live Science.

Broadly, it's intended for those who face major physical barriers to exercising. "We're hoping that this can help all of these cases," said Elgendy, who's also the co-founder of Pelagos Pharmaceuticals, a startup aimed at developing these exercise-mimicking drugs, or so-called exercise mimetics. 

In a video interview, Elgendy added that the medicines would also be useful for those too busy to get enough exercise or who are "lazy, like myself."

Related: 11 minutes of moderate exercise a day cuts early death risk by 20%, huge analysis suggests

In previous research, Elgendy and colleagues found a molecule that turns on these exercise switches in cells in lab dishes and in animals. More recently, they've used that molecule as a starting point to develop new compounds that are more potent at mimicking the cellular effects of exercise. They presented these findings Monday (March 18) at the American Chemical Society's (ACS) spring meeting. The work represents a small step toward bringing these drugs to patients.

"This is an early-stage drug discovery program; it's not complete yet," Elgendy said. "If everything goes well, we're hoping [to start human trials] in the next couple of years."

The researchers' quest began with looking for molecules capable of plugging into structures on cells known as "estrogen-related receptors" (ERRs). These are similar to estrogen receptors in terms of their protein and genetic makeup, but despite their name, ERRs don't respond to the hormone estrogen. Rather, they're orphan receptors, meaning scientists don't know what naturally binds to them, Elgendy said.

However, these receptors can be found throughout the body, and they're particularly important in tissues with high energy demands, like skeletal muscles,the heart and brain. For instance, studies of mice's skeletal muscle suggest activating the receptors helps boost the production of fuel by cells' mitochondria, increase the animals' exercise endurance and help cells switch to burning fats instead of sugars.

ERRs come in three flavors — alpha, beta and gamma — and in the past, scientists had found ways of activating the beta and gamma receptors with human-made compounds. But alpha, known to be very prevalent in the brain and in skeletal muscle, proved difficult to target.

"There was a claim that it was not druggable," Elgendy said. But a new molecule made by the team, named SLU-PP-332, can activate all three flavors of ERRs, and alpha most potently. The researchers described the compound in a previous paper published in March 2023 in the journal ACS Chemical Biology.

In lab-dish studies, the compound boosted skeletal muscle's metabolism, and in mice, it improved the rodents' endurance for running and increased their number of fatigue-resistant muscle fibers.

In their latest work, the team iterated upon SLU-PP-332, designing new molecules that would fit more snugly in the three receptors and have higher potency without risking unintended effects. ERRs have a hand in a variety of cellular functions, and are found in cancerous as well as healthy cells. So as they continue drug development, the researchers will have to check that they're primarily mimicking exercise effects without inadvertently tripping other wires in the body.

The team is now testing their newest generation of molecules in animals. They're starting by studying mice whose biology mimics aspects of human heart failure, obesity and kidney dysfunction, to see whether the new compounds could help treat the conditions.

There's also evidence that the ERR alpha receptor is relevant to Alzheimer's disease, as its activity has been linked to lower levels of misfolded proteins in the brain. Treating Alzheimer's and other neurodegenerative disorders is an avenue the team is interested in exploring, Elgendy said.

However, for now, "this is not a drug," he said. "It's never been tested in humans." The researchers have a lot of work to do to test the molecules in animals, see how they're processed by the body and make any necessary tweaks before moving the candidate drugs into people. "Translation takes a lot of time," Elgendy said.

This article is for informational purposes only and is not meant to offer medical advice.

Ever wonder why some people build muscle more easily than others or why freckles come out in the sun? Send us your questions about how the human body works to community@livescience.com with the subject line "Health Desk Q," and you may see your question answered on the website!

Just 11 minutes of moderate physical activity a day could lower the risk of early death by 23%, a review of data from more than 30 million adults suggests. If everyone could meet this daily target, 1 in 10 early deaths worldwide could be prevented, the study authors propose.

The study, published Tuesday (Feb. 28) in the British Journal of Sports Medicine, is the largest of its kind. Using 196 previously published research articles, Søren Brage, an investigator at the University of Cambridge's Medical Research Council (MRC) Epidemiology Unit, and his colleagues uncovered the relationship between physical activity and risk of death, as well as the risk of specific conditions like heart disease, stroke, leukemia and colon cancer. The studies included in the paper followed participants over an average of 10 years, monitoring their exercise habits and rates of disease and death.

Heart disease is the leading cause of death worldwide, responsible for 17.9 million deaths annually. The new study found that just 75 minutes of physical activity per week, or 11 minutes a day, is linked to a 17% lower risk of cardiovascular disease. The same amount of physical activity was linked to a 7% lower risk of developing cancer, a disease responsible for an average of 9.6 million deaths per year globally.

This level of physical activity per week is half of the amount of exercise recommended by the U.K. National Health Service and in the Physical Activity Guidelines for Americans, which advise that adults complete at least 150 minutes of moderate-intensity activity per week. While the new study found that this higher exercise level had an even greater effect on health — lowering risk of early death by 31% — any activity, of any duration, adds up and is likely to improve health, Brage told Live Science in an email.

Related: Quitting smoking by age 35 brings your risk of death in line with 'never smokers' 

"It is surprising to some just how little things can add up, like taking the stairs instead of the lift, or walking to the local shop instead of driving," Brage said. Activities like brisk walking, dancing, going for a gentle bike ride and playing outdoors count towards your 11 minutes a day, but Brage said the same benefit can be felt by doing vigorous, rather than moderate, exercise for half the time.

"So, if one is time poor and able to do vigorous activity, it is an efficient way to clock up the weekly volume," Brage said. "Vigorous activity includes any activity that elevates your heart rate, makes you sweat, and gets you out of breath, like running or fast cycling."

Anyone hoping to add more physical activity into their daily lives should choose exercises that are realistic and fit within their current lifestyle, said Naveed Sattar, a professor of cardiovascular and metabolic health at the University of Glasgow, who was not involved in the new study.

"Activity that is fun or a necessity — or ideally both — is sustainable," Sattar told Live Science in an email. "Walking 1,000 steps more a day (roughly 10 minutes of activity) is often a good start for many, but you need to find a way to enjoy walking, by listening to a podcast or going with a friend, or by making it a necessity by introducing it into your commute to work," he suggested. 

The study only included activity outside of a person's occupation, meaning a manual laborer who did 75 minutes of physical activity outside of work each week was classed the same as an office worker with the same recreational exercise regime. This was partly because occupational activity is harder to measure precisely, Brage told Live Science. 

"But we also focused on the component of daily life that is likely easier for most people to change; although it is not impossible to change jobs, it is certainly not something you would do very often," he said.

This HoMedics Pro Physio review takes a closer look at this electric massage gun, from testing its features and functionality, to checking out the most recent user reviews. We’ve got everything you need to know, from percussions per minute (PPM) to what sets this massage gun apart from others on the market.

The massage gun features six head attachments, the most of any of the massage guns we tested at home. Boasting a maximum PPM of 3000 PPM, the HoMedics Pro Physio also includes a heated head attachment to deliver warmth to problem areas, and a cool head attachment. 

HoMedics says its massage gun balances relaxation, relief from muscle tension and tight knots, and recovery from exercise in one simple-to-use device. Designed to be used at home or on the move, the massage gun also comes with a carry case to store the gun and head attachments.

And if the HoMedics Pro Physio isn’t the massage gun you’re looking for, our guide to the best massage guns has lots more options for the perfect fit. 

HoMedics Pro Physio review: size and design

The HoMedics Pro Physio comes in a recyclable cardboard box. Inside is a very professional looking carry case, with the HoMedics branding. Within the protective carry case a molded foam holder provides slots for the gun, all six head attachments that come with it, and the plug-in charger. This secures all your attachments and keeps them in good condition.

A mesh compartment in the lid holds the user manual and an explanatory guide on how and where to use the massage gun on the body, complete with which head attachment to use and what intensity to use it at, which is very useful.

The gun itself is fairly heavy, weighing in at 2lbs. This makes it one of the heaviest massage guns we tested at home. Although it’s not uncomfortable to use for longer periods, it could become heavy and unwieldy over longer massage sessions.

When it comes to design, it’s clear that HoMedics have prioritized function over design. The Pro Physio looks a little like a hairdryer, with a long handle and matte black casing. At the rear of the gun, three lights indicate speed settings, while an adjustable ring at the base allows users to turn the motor on and adjust the speed and intensity. The massage gun requires two hands to operate, unlike many others which feature a single button for power and speed. 

Users can select their head attachment and screw it in securely to the opening of the gun, ready for use. At the base of the handle is a port for the charger and a battery indicator.

Six head attachments are included:

• Barrel: For the upper back, calves and forearms
• Ball: For the quads, hamstrings, glutes, feet and hands
• Cool gel: For the IT band, shins and hip flexors
• Heated: For the lower back, traps and glutes
• Cellulite: For massaging areas with cellulite
• Arrow: For targeting problem areas and smaller muscles

The battery is designed to last for an impressive five hours of use, falling to 3.5 hours if you favor the heated head attachment, which uses up more battery life. We weren’t able to test this fully at home, but found the massage gun charged quickly and gave a great performance during all our massage sessions, which totaled around an hour. 

HoMedics Pro Physio review: functionality

The HoMedics Pro Physio features three speed settings, from a lower intensity of 2100 PPM to the highest setting of 3000 PPM. Users can select the setting they feel most comfortable with, or follow the user guide that comes with the gun. This guide tells you which intensity setting to select for which parts of the body, and for how long to use the gun in that particular area. 

There are no connected apps designed for the HoMedics Pro Physio, unlike those that accompany other massage guns such as Hypervolt or Therabody. So users hoping to improve their technique, or follow specific routines by using an app or Bluetooth connectivity, may be disappointed by this. 

The flat heated head attachment is just as easy to attach as the other heads, by screwing it into the opening at the end of the gun. LED lights flash red while it warms up, and stay red once it has reached 47 degrees celsius. This takes around 2 minutes of operation.  During our testing, we noticed that the head loses a little heat during operation and has to warm up again, so some users may be put off by this. 

The cooling gel head needs to be frozen for at least four hours before use, so it’s not the easiest attachment to simply pop on and use. It’s not clear whether the attachment can stay in the freezer on a permanent basis. If not, you’ll have to remember to pop it in at least four hours before you want to use it, which can be a bit of a drag. Once it’s pulsating against the skin, it quickly loses its cooling ability too, so we’re not sure how useful this attachment is. 

HoMedics Pro Physio review: performance

As with all our massage gun tests, we tested the decibel levels of each setting to see how noisy the HoMedics Pro Physio could be during operation. The gun comes with three speed settings:

Level 1: 2100 PPM
Level 2: 2400 PPM
Level 3: 3o00 PPM

At level 1, using the heated flat head attachment, the gun clocked in at 45 decibels. Level 2 was 50 decibels and level 3  was around 54 decibels. These are all around the same levels as a quiet library, normal conversation, or moderate rainfall. So while the HoMedics Pro Physio may be a little distracting in a quiet office area, it should be fine to use in a busy gym or while watching TV, without disturbing others too much.

HoMedics Pro Physio review: what’s good about it?

It was a simple addition, but we appreciated the fold out user guide that came with the massage gun. It clearly defined the target muscle group, what level the massage gun should be used at, and what type of head attachment should be employed for this area. It even offered tips on how long to massage for, and how many repetitions were needed. In the absence of a companion app or video tutorials, this was clear, well laid out and useful to refer to. 

We also enjoyed the heated head attachment. This felt super soothing on the glutes and quads after a run, and helped to relax tight lower back and shoulder muscles after a day spent hunched over at a desk.

HoMedics Pro Physio review: what’s not so good about it?

Compared to smaller, lighter massage guns, such as the Recovapro Lite or the Hypervolt Go, the HoMedics Pro Physio feels like a bit of a beast. We found it a little unwieldy to start with, and we did get tired moving it around awkward and hard-to-reach areas during longer massage sessions. 

While we had hoped to use the cool attachment after every jog or gym session, it wasn’t clear whether you can keep the attachment in the freezer permanently, to keep it cool. So you have to remember to pop it in the freezer at least four hours before you intend to use it, which is easy to forget. 

HoMedics Pro Physio review: User reviews

The HoMedics Pro Physio gets an impressive 4.9 stars out of five on its website from happy users. They particularly like the heated head attachment, the carry case, and the arrow head for targeting problem areas. One user said it has “done wonders for my shoulder and back after just a month.”

The massage gun also scores highly on Amazon, with 4.5 stars out of five. Although they like how sturdy and well-made the HoMedics Pro Physio is, some users do find it a little heavy during longer periods of use. 

Should you buy the HoMedics Pro Physio?

The HoMedics Pro Physio could be a good investment if you’re interested in using warmth and coolness to tackle muscle strain and tension, as well as massage. The massage gun is well-made, sturdy and performs well during testing. It’s a solidly performing piece of kit, if somewhat lacking in style. 

It’s easy to operate, and the user guide that’s included means you can develop and adapt your own routines instead of following along on a connected app or video tutorial.

However, it’s not the most portable of devices, so if you’re looking for something to throw in the gym bag at a moment’s notice, you may prefer something lighter.

If this product isn’t for you

If you want a massage gun that you can take anywhere, then why not try the Hypervolt Go? It comes with two attachments, and at 1.5lbs is lighter and smaller than the HoMedics Pro Physio.

If you’d like a massage gun that you can match to your gym kit, the Recovapro Lite comes in a range of fun colors, such as pink, silver, black and blue. It also comes with four attachments and an attractive carry case.

If you’re after a high-performance piece of kit, the Hypervolt 2 combines a powerful performance with a helpful app, to help you target your massage techniques and get the best results.

You've probably heard you need to exercise for 30 minutes a day to be healthy, but if you make your workouts more intense, you may be able to get away with spending much less time working up a sweat.

The "30 minutes a day" rule comes from the current U.S. government exercise guidelines, which recommend that people engage in 150 minutes of moderate-intensity aerobic activity per week. (This works out to about 30 minutes a day, five days a week.) But the key word here is "moderate" exercise. If your workouts involve vigorous exercise, they can be shorter, experts say.

"You can get more bang for your buck with vigorous exercise," said Dr. Edward Laskowski, co-director of Mayo Clinic Sports Medicine in Rochester, Minnesota.

Specifically, new research suggests that a type of workout known as interval training may allow people to get fit in much less time than is required with traditional endurance exercise. Interval training involves the following steps: warm up for a few minutes, go "all out" for about 30 seconds, recover at a slow pace for a few minutes and then repeat this cycle several times before cooling down.

A recent study found that a 10-minute interval training workout, which involved just 1 minute of total sprinting time, was just as good as a 50-minute endurance workout done at a moderate pace in terms of getting people fit. Men in the study who did the interval-training workout showed similar improvement in aerobic fitness, metabolism and muscle function as men who did the endurance workout.

"This is good news for a lot of people," Laskowski said. "We can really get a good training effect in a shorter period of time" with interval training, he said. Laskowski recommended that people warm up for about 3 minutes, do about three to four interval cycles, and then cool down. This would take about 17 minutes if a person did four 30-second intervals of intense exercise, with 3 minutes of rest in between each, and a 3-minute warm-up and cooldown. [How to Start an Exercise Routine and Stick to It]

Although studies are finding that interval training may offer similar fitness benefits as endurance workouts, researchers still need to conduct more studies on the long-term effects of interval training, Laskowski noted.

But studies have found that interval training can be tolerated by lots of different groups, including people who are obese or have heart disease, Laskowski said. Some studies have even found that people enjoy interval training more than traditional endurance training.

"People seem to like high-intensity interval training because it is efficient and effective also," Laskowski said.

Still, it's a good idea to see your doctor before you start interval training. Some types of exercise may not be good to perform at high intensities, Laskowski said. For example, running may not be good for people with knee arthritis, because this activity is hard on the joints. But people with knee arthritis may still be able to do interval training on a bike or in the pool without damaging their joints, Laskowski said.

Follow Rachael Rettner @RachaelRettner. Follow Live Science @livescience, Facebook & Google+. Original article on Live Science.

If you think you don't have time to exercise, there's good news: Short bouts of activity — as brief as a few minutes each — may still have health benefits, as long as they add up to 30 minutes a day total, recent research suggests.

Traditionally, experts have recommended that people exercise for at least 10 minutes at a time, at a moderate pace. But these recommendations are based on earlier studies that asked people to remember how much time they spent being active each day. Since people have trouble remembering very short activities, it was hard to study whether smaller amounts of exercise could improve your health, said Brad Cardinal, a kinesiology professor at Oregon State University.

But newer technologies, like the accelerometers found in most fitness trackers, allow researchers to more accurately measure people's daily activities. And that's showing that even short bursts of activity, like vacuuming or walking up the stairs, can be good for you.

"The way physical activity is being measured is a little more precise than it used to be," Cardinal told Live Science. "As we start to use this newer technology, we're starting to see the benefits of these shorter bouts of activity." [How Many Calories Am I Burning? (Infographic)]

For example, in a 2013 study, Cardinal and colleagues analyzed information from more than 6,000 U.S. adults who wore accelerometers for at least four days. Results showed that people who exercised in bouts of 10 minutes or less, but who accumulated enough activity to add up to 30 minutes a day, fared just as well in terms of health as people who exercised for longer periods. Health was measured by key markers, such as blood pressure, cholesterol levels and waist size.

"The health benefits were essentially the same" between the groups, Cardinal said.

Another study looked at the fitness levels of people who didn't engage in any traditional exercise, like jogging or going to the gym, but who wore accelerometers around their waists for a week to track their movements. None of those participants met the physical activity guidelines, which advise people to get 150 minutes of moderate physical activity per week, achieved through bouts of exercise that are at least 10 minutes.

But on average, the participants accumulated about 20 minutes of moderate exercise daily simply by doing activities like climbing stairs or doing household chores.

The more time people spent on these so-called "incidental" physical activities, and the more intense the activity was, the better the individuals' fitness levels, the study found. The researchers estimated, based on markers of the participants' fitness, that a 30-minute increase in moderate physical activity achieved through everyday activities could reduce the risk of cardiovascular disease by 15 percent.

"It's encouraging to know that if we just increase our incidental activity slightly — a little bit more work around the house, or walking down the hall to speak with a co-worker as opposed to sending an email —we can really benefit our health in the long-term," study co-author Ashlee McGuire, a physical activity researcher at Queen's University in Canada, told Live Science in a 2011 interview.

Cardinal said that people may be more likely to stick with a physical activity routine that involves short bursts of exercise. For example, six 5-minute bouts of activity throughout the day may sound less intimating to some people than a 30-minute workout done all at once, Cardinal said.

It's not clear whether short bouts of activity can help people lose weight, so more research is needed to look at that question.

Follow Rachael Rettner @RachaelRettner. Follow Live Science @livescience, Facebook & Google+. Original article on Live Science.

If you hate to exercise, you may benefit from a type of talk therapy that helps people accept negative feelings and uncomfortable sensations.

Several recent studies suggest that this therapy, called acceptance and commitment therapy (ACT), can boost people's physical activity levels and improve fitness in those who previously didn't exercise at all.

ACT teaches mindfulness, which means that it aims to make people more aware of their thoughts and feelings in the current moment. People learn how to accept uncomfortable physical sensations and metaphorically "make room" for these feelings in their bodies, according to a 2015 study of ACT in Australia. They also learn to question whether a thought (such as "Exercise is intolerable") might be getting in the way of their goals, and learn to see these thoughts for what they really are — just thoughts, as opposed to concrete facts.

People also learn to identify their core values and are encouraged to engage in behaviors that support these values. Identifying the value, or meaning, behind a behavior may help people commit to that behavior, said Emily Cox-Martin, an assistant professor of medicine and clinical psychologist at the University of Colorado's Anschutz Medical Campus who conducted a 10-week study of ACT on sedentary adults.

For example, if someone says they want to be stronger so they can play with their grandchild, "this indicates that being an active grandparent is important to them, and that value can then be connected to the behavior [exercise] in a way that facilitates its maintenance," Cox-Martin told Live Science.

Cox-Martin noted that ACT "isn't trying to change people's thoughts about exercise." Rather, "it helps someone understand what they value in life, and then how they can live a life consistent with those values," she said. [How to Start an Exercise Routine and Stick to It]

In Cox-Martin's study, which was published in October 2015, the researchers tested the ACT-therapy strategy with 24 previously sedentary adults. All of the participants were taking part in a fitness program that involved starting up an interval training program — exercising three times a week — and receiving ACT.

The researchers found that over 10 weeks, the participants completed almost all of the exercise sessions that they were asked to do (27 out of 30 sessions, on average). They also improved the time it took them to walk a mile by more than a minute, and increased their VO2 max, a measure of aerobic fitness level.

One limitation of that study was that there was no control group. In other words, the researchers did not compare the results of the group who received ACT with another group that did not receive ACT. However, the researchers said the study showed that it was feasible to use ACT to help people reach higher levels of physical activity.

The Australian study involved 59 adults who were doing only minimal amounts of physical activity. Researchers recruited them to participate in a 12-week program that aimed to get them to walk more. About half of the participants received a DVD that instructed them in ACT, while the other half didn't receive any training in ACT. At the end of the study, the participants in the ACT group were four times more likely to meet exercise guidelines in Australia (taking 3,000 steps in 30 minutes, five days a week) than people who didn't receive the ACT training.

"The discomfort associated with physical activity initiation can be a strong contributor to premature termination" of exercise, the researchers, from Australian Catholic University and the University of Adelaide wrote in the February 2015 issue of the British Journal of Health Psychology. "[ACT] allows the individual to tolerate discomfort, accept uncomfortable experiences, and facilitate progress towards goals." 

However, more research is needed to determine whether the benefits of ACT seen in these early studies last over the long term, and whether the findings will hold in larger studies with more diverse populations.

In addition, studies will look into whether programs that teach ACT can be adopted on a wider scale, so that people may be able to learn these skills at home or through a smartphone app, rather than participate in a formal program.

"Acceptance and commitment therapy has already been used to help people change other health behaviors, like smoking cessation, using smartphone apps, and this would be a really interesting next step, especially given how widely used this technology is today," Cox-Martin said.

Follow Rachael Rettner @RachaelRettner. Follow Live Science @livescience, Facebook & Google+. Original article on Live Science.

In 2015, a panel of experts in sleep, anatomy, physiology, pediatrics, neurology, gerontology and gynecology joined forces to create new, age-specific sleep recommendations.

Low carb, or low fat? Should you go Atkins, Zone or Paleo? Or does it even matter which diet you choose when you want to lose weight? Most weight loss experts say that shedding pounds comes down to a simple formula: calories in versus calories out. In other words, if you burn more calories than you take in, you'll lose weight.

However, the question of exactly how to cut calories — in a healthy, sustainable way — has often perplexed dieters. To find the best diets for weight loss, Live Science conducted a months-long search for information. We spoke with many weight loss experts and dove deep into the most well-regarded studies on the topic done to date. We wanted to know what these studies found and, ultimately, determine the best approaches to healthy eating for weight loss.

We found that the calorie equation reigns supreme as the most important aspect of losing weight, but also that there's still plenty of room to choose a diet that fits your personal preferences. For example, Dr. Frank Hu, a professor of nutrition and epidemiology at the Harvard University T.H. Chan School of Public Health, told Live Science that "the No. 1 factor is still a calorie deficit, so the question is, what kind of styles or what kind of foods can help people achieve a calorie deficit, and what can sustain the calorie deficit?" [What Are Calories?]

(What all experts did not agree on, however, was the calorie question: Is a calorie really a calorie?) [The Great Calorie Debate]

So, what should you eat if you're trying to slim down?

"The best food someone on a diet should eat? The same foods they should eat when they're not on a diet, but just less of them," said Dr. Frank Sacks, a professor of cardiovascular disease prevention, also at Harvard's School of Public Health. All of the experts we spoke with agreed that those foods should include the staples of a "healthy" diet — fruits, vegetables, whole grains and healthy fats. These foods are important not only for achieving or maintaining a healthy body weight but also for good health in general.

In this article, we'll highlight some of the most popular diets people turn to in order to lose weight, and explain what the science really says about how well they work. But before we delve into the diets, it's important to break down the macronutrients of the foods we eat — carbohydrates, fats and protein — and the roles they play in the body. Of course, individual food can contain more than one more macronutrient.

Back to basics

Carbohydrates

Carbohydrates are your body's go-to source of energy, and they're digested quickly. Glucose — the most basic unit of a carbohydrate — is the only type of carb your cells can use directly to make energy. But the carbs we eat come in three forms — sugars, starches and fiber — and when it comes to weight loss, these three are not equal. [What Are Carbohydrates?]

Sugars (found in fruit, vegetables and dairy) and starches (found in grains, vegetables and beans) ultimately suffer the same fate: They're broken down into glucose and are used by the body for energy. But your body can use only so much energy at once, so not all of the glucose you eat is immediately used for fuel. Some of the extra glucose can be stored in your liver or muscles and be used later.

As for the rest? It gets converted to fat.

The difference between sugars and starches — which are sometimes referred to as "simple" and "complex" carbohydrates, respectively — is the complexity of their structure. Sugarscontain only one or two molecules, so it's very easy for the body to digest sugars and absorb them into the blood. Starches, in contrast, contain many simple carbohydrate molecules linked together. Because of their size and complexity, starches take longer to be digested into single molecules.

Fiber is an entirely different ball game. Fiber is found alongside sugars and starches in fruits, vegetables, whole grains and legumes. Like starch, it's a complex carbohydrate, meaning it contains many carbohydrate molecules linked together. However, your body can't digest fiber, so this carbohydrate doesn't get absorbed by the gut. It never enters the bloodstream, and it is never broken down for energy. The stuff passes through your body relatively untouched.

The benefit of eating starches, and especially fiber, rather than sugars is that they can help you feel fuller for a longer time because they are either broken down slowly or aren't broken down at all. And the idea is, if you're feeling full, you'll eat less. Of course, keep in mind that complex carbs aren't a free pass to eat as much as you like — extra calories consumed will still be stored as fat.

Compared with fat, carbohydrates are less calorie-dense: 1 gram of carbohydrates contains 4 calories, whereas a gram of fat contains 9 calories. However, because carbohydrates are broken down and absorbed quickly, they can lead to a quicker burst of sugar into the bloodstream than fat does. Therefore, carbs may raise blood sugar levels more than fat does (when compared in equal amounts).

Proteins

Protein-rich foods are important for everyone, not just bodybuilders. Protein serves as the building blocks for our bodies, from the tiniest structures inside our cells, to the largest parts of our anatomy. Unlike carbs or fat, excess protein isn't readily stored by the body, so it's essential to eat enough of this macronutrient every day. Of course, just because your body doesn't store the protein doesn't mean you have free rein to eat as much as you'd like without gaining weight. The body can convert excess protein into glucose, or store it as fat.  [What is Protein?]

When you eat protein, the large protein molecules are broken down into their basic components, which are known as amino acids. There are 20 amino acids that are important in the body, and some can be converted from one type of amino acid to another as needed. However, there are also several amino acids that cannot be produced in the body by converting other amino acids, meaning you must get these amino acids from your diet. These are known as essential amino acids.

Both animal-based proteins (such as those found in meat, fish, dairy and eggs) and plant-based proteins (found in soy, legumes, nuts and some grains) contain essential amino acids. However, whereas all animal-based proteins contain all of the essential amino acids your body needs, plant-based proteins generally contain a smaller set of amino acids. That means that if you eat a vegan diet, you need to eat a variety of plant types to get all of your essential amino acids.

As with carbohydrates, 1 gram of protein contains 4 calories. 

Fats

Fat does more than pad your waistline — in fact, your body needs some fat to function. For example, in addition to being a reserve source of energy that can be taken out of storage and converted into glucose if needed, fat can help your body absorb certain vitamins. And because fat is broken down more slowly than carbs, it can also help you feel full longer than carbs can.

But there's no doubt that fat is high in calories. In fact, it's the most calorie-dense of the macronutrients, weighing in at 9 calories per gram.

Of course, like carbs, not all fats are created equal. Unsaturated fats are typically found in fats that are liquids at room temperature — oils such as olive oil and canola oil — as well as foods such as nuts and fish. These fats are considered heart healthy, and can certainly be considered a part of a healthy diet for weight loss.

But saturated fats (such as butter), which are usually solid at room temperature, and trans fats (such as hydrogenated oils) are largely considered unhealthy, mainly because of their effects on heart health.

Fat that goes unused by the body ultimately has the same fate as carbs and protein: It's stored as fat.

The macronutrient wars

Though all three macronutrients — carbs, protein and fat — are essential to your diet, there's debate about exactly how much of each you should eat. Should carbs be the star of your diet, and fat be consumed sparingly? Or should fat be fronted-loaded? Or do the relative amounts of macronutrients in your diet even matter at all?

There's an abundance of advice in books, magazines and online sources about the best way to diet, and there are anecdotes about the diet "trick" that worked miraculously for someone's mom's best friend's former next-door neighbor to be found everywhere. But how do we know if they actually work?

Enter clinical trials, which allow researchers to directly compare the effects of different diets. And even among these trials, some are better designed than others. Researchers consider many factors when looking at the quality of a trial, including the size of the trial (the more participants, the better) and the length of the study period (the longer, the better), when deciding how much stock to put into the results.

The largest clinical trial that compared different diets was the Women's Health Initiative (WHI) Dietary Modification Trial, which included more than 48,000 postmenopausal women and had a follow-up period of seven years. However, the trial was not designed to look at weight loss. Rather, the goal of the trial was to see how fat in the diet affected the women's risk of cancer and heart disease. (Because the trial was only in women, it's unclear if the results also apply to men.)

The WHI Dietary Modification Trial was designed in 1990, when researchers were asking many questions about whether high-fat diets or low-fat diets were better for people's health, said Barbara Howard, a senior scientist at the Georgetown University Medical Center in Washington D.C. In a study published in the Journal of the American Medical Association (JAMA) in 2006, Howard took data from the original WHI Dietary Modification Trial and looked to see whether the two diets had different effects on weight loss.

In the WHI, 40 percent of the participants were encouraged to reduce their fat intake so that only 20 percent of their total daily calories came from fat. (At the study's start, all of the participants had reported that at least 32 percent of their daily calories had come from fat.) The women were encouraged to increase their daily servings of fruits, vegetables and whole grains, and attended group sessions where they got advice about cutting fat. However, because the trial wasn't designed with weight loss in mind, these women were not encouraged to cut calories.

The other 60 percent of the women went into the control group. They were given a copy of the U.S. government's Dietary Guidelines for Americans and some additional educational material, but that was it. [Low-Fat Diet: Facts, Benefits & Risks]

The researchers monitored the diets of all of the participants during the study through questionnaires, and measured the women's height and weight at annual checkups.

It turned out that the women in the low-fat-diet group lost a little bit of weight over the course of the study period, and they maintained their weight loss, said Howard, who is also a scientist at the MedStar Research Institute, a non-profit healthcare system of hospitals and clinics in the Washington D.C. area.

The researchers found that the women in the low-fat-diet group lost about 5 lbs. (2.2 kilograms) during the first year of the study, and then maintained a lower average weight than the control group over the rest of the study period.

The researchers concluded that there was a "clear relationship" between the change in the women's fat intake and their weight, they wrote in their study. The questionnaires showed that the women in the low-fat-diet group increased their daily intake of fiber, fruits, vegetables and whole grains, and decreased their daily intake of total fat, saturated fat and unsaturated fat. [Which States Are Eating Their Fruits and Veggies?]

In particular, the women who cut the most fat lost the most weight, the researchers found. 

Also, the women in the low-fat-diet group who ate more fruits and vegetables also lost more weight than those whoate smaller amounts of fruits and vegetables, the researchers found. The same went for fiber: The women who ate more fiber lost more weight than the women who ate less fiber.

Another long-running clinical trial designed to compare the effects of different diets on weight loss was carried out in Israel: the Dietary Intervention Randomized Controlled Trial, or DIRECT, study.

But although that large, high-quality study found a relationship between a low-fat diet and weight loss, other studies conducted since have found that a low-fat diet is no more effective than other types of diets in helping people lose weight. It's important to note that the women in the study who switched to a low-fat diet didn't replace the fat in their diet with white bread and other refined carbohydrates, Howard said. In other observational studies, researchers have shown that when "high-carb" means sugar and refined carbohydrates, people don't lose weight, she noted.

The trial included 322 people, ages 40 to 65, all of whom were overweight and worked at the same research center. The participants were randomly assigned to different diets — a low-fat diet, a Mediterranean diet or a low-carb diet — for a two-year period. The researchers also conducted a follow-up four years after that, so the total study period was six years. The participants in the low-fat diet group and the Mediterranean-diet group were instructed to cut their calories, while those on the low-carb diet were given no calorie restrictions.

As in the WHI study, the participants received diet guidance in small group sessions. (One key difference between the two studies, however, was that in the DIRECT study, everyone was assigned to a group session.) In addition, because all of the participants worked at the same place, the researchers provided lunch each day. Each diet group was given a lunch that fit their diet, according to the report of the study, published in 2008 in The New England Journal of Medicine.

But unlike in the WHI study, the low-fat diet in the DIRECT study didn't result in the most weight loss. Rather, weight loss was the highest in the low-carb group — the participants in this group lost an average of 12.1 lbs. (5.5 kg) after two years. The participants in the Mediterranean-diet group lost, on average, 10.1 lbs. (4.6 kg), and the participants in the low-fat group lost, on average, 7.3 lbs. (3.3 kg) after two years. [Low-Carb Diet: Facts, Benefits & Risks]

Additionally, there was a difference in which diets were the most effective for each sex. The women in the study who were on the Mediterranean diet lost more weight than the women on the low-fat diet. In comparison, the men on the low-carb diet lost more weight than the men on the low-fat diet, the researchers found. (However, only 45 women completed the study, compared with 277 men.) In other words, both women and men lost more weight on a diet other than the low-fat diet.

The DIRECT study showed that one diet doesn't fit all, said Iris Shai, a professor of nutrition and epidemiology at Ben-Gurion University of the Negev in Israel and the lead author of the study. In other words, the researchers learned that there are some alternatives to a low-fat diet that also work for weight loss, Shai told Live Science. These alternatives (the low-carb diet and the Mediterranean diet) also have more health advantages in the long run, such as improved cholesterol and blood sugar levels, respectively, she said.

However, Shai noted that even though the people on the low-carb diet were not given a calorie restriction, they ended up eating a similar number of calories as the people in the calorie-restricted groups, Shai said. Ultimately, all of the groups cut their calories by about 400 to 500 calories a day, she said. In other words, the study suggested that calories do matter for weight loss.

In the follow-up four years later, the researchers found that all of the participants had regained some of the weight. Over the entire six-year period, the average total weight loss was 6.8 lbs. (3.1 kg) for the Mediterranean-diet group and 3.7 lbs. (1.7 kg) for the low-carbohydrate group. The average weight loss of 1.3 lbs. (0.6 kg) for the low-fat group was not statistically significant, meaning that the finding could have been due to chance, the researchers wrote.

One reason the Mediterranean diet appeared to be the most effective for weight maintenance is that, simply put, in real life, a more "balanced" diet that offers many options may work best in the long term, Shai said.  [Mediterranean Diet: Foods, Benefits & Risks]

Dr. George Bray, a professor emeritus at Pennington Biomedical Research Center at Louisiana State University and the founder of The Obesity Society, agreed.

"I'm a fan of using a high-quality, good-pattern diet with lower amounts of food, and one way of doing that is with portion control," Bray said. Plenty of evidence suggests the Mediterranean diet is highly beneficial for people's health and, combined with portion control, is a good strategy for weight loss, Bray told Live Science. The DASH diet, which was developed to lower blood pressure, also has shown weight loss benefits, he said. The DASH diet is a low-sodium diet that's rich in fruits, vegetables, low-fat dairy, nuts, beans and seeds.

"As far as I can see, nothing else is of value," Bray told Live Science. "It comes down to calories — pure and simple."  [Best Calorie Counter App]

Bray was one of the authors on another major weight loss study, called the Preventing Overweight Using Novel Dietary Strategies study, or the POUNDS Lost study. The results of that study were published in 2009 in The New England Journal of Medicine.

In that study, two teams of researchers — one in Boston and one in Baton Rouge, Louisiana — carried out the randomized trial, which was — and still is — the largest clinical trial designed to compare the weight loss effects of different diets. (The study had more participants than the DIRECT study, although the study period for the POUNDS Lost study was shorter.)

The POUNDS Lost study began with more than 800 participants (400 in Boston, and 400 in Baton Rouge) who were randomly assigned to one of four diets: low-fat with average protein, low-fat with high protein, high-fat with average protein and high-fat with high protein. A total of 645 people completed the study.

The people in the study were assigned to counseling sessions to learn about their diets, and there were group sessions held throughout the course of the study. The researchers provided the participants with daily meal plans, and the plans were largely similar across the four diets, with only small tweaks — for example, to include a bit of extra olive oil, or a bit less meat. All of the diets in the study were healthy — they all contained healthy fats, whole grains, fruits and vegetables, said Sacks, who was the lead author of the study. And all of the diets contained an equal number of calories — fewer than the number of calories the people in the study were normally eating, he said. [2016 Best Food Scales]

So, how did the different diets stack up for weight loss?

The main takeaway of the study is that all of the diets produced the same amount of weight loss, Sacks said. "There was no advantage of one diet type over another," he said. The researchers observed that, at six months, the participants in each diet had lost, on average, 13.2 lbs. (6 kg). After the one-year mark, on average, the participants began to regain some of their weight. By the end of the study, the average weight loss for all of the diets was 8.8 lbs. (4 kg).

Bray, who ran the Baton Rouge arm of the study, noted that there was certainly a range for the weight loss observed among the people on each diet. However, the range was similar in all of the groups, he said. Some people on each diet lost as much as 33.1 lbs. (15 kg), and some people on each diet gained a bit of weight, Bray told Live Science. But even the proportions of people losing a lot of weight or gaining a little weight were similar in all four diets, he said.

The biggest factor for weight loss? Undoubtedly, it was adherence to the diet, Bray said. "If you stuck to [the diet] well, you should lose more, and if you didn't stick to [the diet], you shouldn't," Bray said.

Putting it all together: Meta-analyses

Of course, it's important to keep in mind that, while these three trials have revealed some of the best evidence yet about weight loss strategies, countless smaller or shorter clinical trials have focused on diet and weight loss. To truly get a sense of the state of the field of research, scientists look at many studies together, in a type of study called a meta-analysis. This type of research can be especially valuable when looking at a number of smaller clinical trials because it reveals what the studies show when they are combined as a whole.

A meta-analysis lets researchers examine a large number of smaller studies to see if, collectively, there's been an impact, Bray said. And when you do that with weight loss trials, you don't come out with any notable differences between diets, he said.

A 2014 meta-analysis, published in JAMA, looked specifically at named diets — for example, the Atkins diet, the Ornish diet and others — and found that both low-fat and low-carbohydrate diets resulted in weight loss. There were 48 studies included in the meta-analysis, and between the individual named diets, the differences in weight loss were small, according to the researchers. 

Both low-fat diets and low-carb diets resulted in about 18 lbs. (8 kg) of weight loss after six months, according to the study.

And while there were some statistically significant differences in weight loss between some of the diets (for example, after six months, the Atkins diet was associated with a 3.7-lb. (1.7 kg) greater weight loss than the Zone diet), "these differences are small and likely to be unimportant to many seeking to lose weight," the researchers wrote in their study. [2016 Best Online Diet Services]

"The main takeaway [of the meta-analysis] is that there's really no important differences between any of the diets," said Bradley Johnston, the director of Systematic Overviews through advancing Research Technology at the SickKids Research Institute in Toronto and lead author of the meta-analysis.

Indeed, most of the diets that Johnston looked at seemed to come back to calories.

Whether people did low-carb or some other type of diet, most of them were calorie-restricted, Johnston told Live Science. "If you actually follow the diet, it's highly likely that you're going to lose weight," he said.

What's important is that people choose a diet that they can stick with.

"Adherence is crucial," Johnston told Live Science. Because different people have an easier time sticking to different diets, the ideal diet is the one that the individual can adhere to best, so that they can stay on the diet as long as possible, the researchers wrote in their study. And in smaller studies, healthy eating habits have been linked with not only weight loss but also improved health, such as lower blood pressure, lower cholesterol levels, lower blood sugar levels and even improved cognitive function.

In another meta-analysis, published in October 2015 in the journal The Lancet, researchers concluded that low-fat diets were no better than other types of diets evaulated for long-term weight loss. The researchers looked at 53 studies that had weight loss as a goal, as well as other studies for which weight loss was not the primary goal (think back to the Women's Health Initiative study, for example).

When comparing weight loss trials specifically to one another, the researchers found that low-carbohydrate diets resulted in greater weight loss than low-fat diets. For both the weight loss trials and the other trials, the researchers found that higher-fat diets resulted in greater weight loss than low-fat diets. And low-fat diets only resulted in greater weight loss when compared with a person's usual diet, according to the study. 

But none of the diets blew the others out of the water. The big picture that people can take away from this meta-analysis is that a low-fat, high-carb diet is not more effective than any other weight-loss diet, said Hu, who was the senior author of the study.

And the amount of weight loss induced by any of the diets was not very impressive, Hu added. Most people regained the weight they lost in six months to a year, he said. Studies have shown that many people tend to regain lost weight over time, and experts think that more research is needed on how to keep weight off successfully. "A low-carb diet may be a little bit more effective than a low-fat diet, but in the long run, both diets are not significantly different from each other in terms of weight loss," Hu told Live Science.

Because many diets produce similar results for weight loss, it's time to go beyond looking at macronutrients for weight loss, Hu said. Now, the focus should be on the quality of the foods that are eaten, he said. The majority of studies focus on macronutrient composition without paying attention to the quality of foods, he said.

And quality counts — people who eat a lot of refined starches and added sugars are more likely to feel hungry and regain their weight because these foods aren't satiating, Hu said. "On the other hand, if you eat a healthy diet with high-quality foods like fruits and vegetables, high-fiber whole grains and [healthy fats such as] avocados and nuts," you may be able to lose more weight and also sustain your weight loss with that kind of diet, he said. [Best Diet and Nutrition Apps]

Of course, if you really want to lose a lot of weight in a short amount of time, you can cut one-third or one-half of your total calories. But although that can be a very quick fix, the problem is that a quick fix usually doesn't last very long, Hu said.

For longer-term weight loss, people need to think about their overall diet patterns and gradually adapt to these patterns so they can stick with them, he said.

This article is part of a Live Science Special Report on the Science of Weight Loss. It will be updated whenever significant new research warrants. Note that any significant change in diet should be undertaken only after consultation with a physician. 

Follow Sara G. Miller on Twitter @SaraGMiller. Follow Live Science @livescience, Facebook & Google+. Originally published on Live Science.